Atherosclerosis is prevalent in all developed nations and is the leading cause of death and disability in the United States. A debilitating and disabling sequela of atherosclerosis is peripheral arterial disease (PAD). Persons with PAD often have impaired function and quality of life, regardless of symptoms. For those with severe PAD, often lower extremity bypass grafting remains the only option for limb salvage.
The gold standard conduit for infrainguinal bypass grafting is autologous vein. While the patency for infrainguinal vein grafts remains approximately 70% at 5 years, vein is not available in approximately one-third of patients due to intrinsic venous disease or prior vein harvesting. In these cases, expanded polytetrafluoroethylene (ePTFE) grafts are the most commonly used alternative bypass conduit. However, the primary patency rates for infrapopliteal ePTFE bypass grafts are dismal. Prosthetic bypass graft failure occurs secondary to either progression of atherosclerotic disease, thrombosis, or development of neointimal hyperplasia.
Problems associated with using prosthetic grafts are so severe that cardiac surgeons do not use them for coronary artery bypass grafting (CABG). Patients that require CABG would benefit significantly from off-the-shelf prosthetic grafts as often times they do not have healthy veins or arteries to perform the procedure. Although ePTFE grafts are the current standard for prosthetic infrainguinal bypass grafting, they can be thrombogenic, especially when used in small diameter below-knee revascularization procedures. Stenosis due to neointimal hyperplasia remains a challenge to their long-term efficacy.
Several types of surface modification strategies have been utilized to change the nature of the interaction between blood and the prosthetic graft. Most of these strategies have focused on permanently immobilizing an antithrombogenic compound or creating a protein-resistant surface, with variable results. For example, heparin has been widely used as an antithrombotic and antiproliferative agent to modify the surface of vascular grafts in order to reduce thrombus formation and neointimal hyperplasia. In animal models, heparin-modified ePTFE grafts significantly reduced acute thrombosis and anastomotic neointimal hyperplasia. However, the possible formation of antiplatelet antibodies and the associated heparin-induced thrombocytopenia can result in deadly outcomes.
Therefore, there exists a need for improved graft modification technologies which enable treatment or inhibition of neointimal hyperplasia while avoiding systemic or toxic side effects.